Our previous research has demonstrated that antibodies in the sera of halothane hepatitis patients react with trifluoroacetylated rat liver microsomal proteins of 100 kDa, 80 kDa, 63 kDa, 59kDa, 58 kDa, 57kDa, and 54 kDa. These findings suggest that similar trifluoroacetylated proteins are the immunogens responsible for the formation of the patients' antibodies and the subsequent development of hepatitis. This year the 58 kDa protein has been purified from liver microsomes of halothane treated and untreated rats. The amino acid sequences of the N-terminal of the protein and of several tryptic peptides showed 100% homology with the encoded sequence of a CDNA isolated from a rat basophilic leukemia cell (RBL-1) that corresponded to phosphoinositide specific phospholipase-C (PI-PLC) isozyme I (a). Moreover, an antibody raised in rabbits against the 58 kDa protein was used to show by immunoblotting that a 58 kDa was present in RBL-2H3 cells, further suggesting that the 58kDa protein is PI-PLC isozyme I (a). These results indicate that PI-PLC is a potential target of reactive metabolites of drugs and as a consequence might either become immunogenic or have its biological activity altered.